1Stig Morten Borch, pHealth2009 ICT

In vitro diagnostic platforms of the future; technological possibilities and challenges

Stig Morten Borch and Liv Furuberg, Microsystems and Nanotechnology,

SINTEF ICT, Oslo, Norwaywww.sintef.no/microsystems

pHealth2009June 25. 2009, Session 1:

Medical sensors and sensor systems

2Stig Morten Borch, pHealth2009 ICT

In Vitro Diagnostics (IVD):Analysis of samples drawn from patients

Blood Whole Blood, Serum or PlasmaUrineStoolSecretion fluids

SalivaGastric juiceMucous secretion

Tissue samplesTissue fluids

Spinal fluidSynovial fluid

Mucous membranes

Microorganisms, Proteins, DNA/RNA, Lipids, Nutrients, Drugs, Hormones,…

3Stig Morten Borch, pHealth2009 ICT

Point of Care IVD platformsDoctors officesNursing homesRemote testing

In field / off shoreAmbulanceHome testingHospitals;

Children’s clinics BedsideEmergency wardsAcute careSurgery rooms

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Clinical use of PoC IVD products:

Infections, Cancer,..Relapse

Anticoagulant therapy, Diabetes, Rheumatic disease, Cancer,..

Disease / treatment monitoring

Diabetes, Infections, Cardio vascular disease / AMI, Cancer,…

Specific diagnosis

Ongoing inflammations, Fibrinolysis,..Detection

Cancer, Cardio vascular disease,…Risk screening

ExamplesClinical use

5Stig Morten Borch, pHealth2009 ICT

Many POC IVD systems at the market CartridgeCartridge + Instrument+ Instrument

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Critical features of PoC IVD platforms for the future:

Compactness (Cartridge + apparatus)

Minimal room for storage

Completely self-contained system

Ease of useIntegrated sample processingAutomated processing and measurements

Minimally invasive samples Fingerprick blood, saliva, urin

Simple three steps procedure; Add sample - Push button - Read result

Result < 5 minutes

Broad application platform – menu+ high sensitivity parameters Flexibility: Assay principles and sensitivity range.

RobustnessPhysicalChemical (e.g. room temp storage)

Reliability and safety: Performance = Ref-.lab. Assay

Low cost

Built in auto-calibration and fail safes

Safe and adequate read out, interfaces, communication, data storage and connectivity.

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Detection systems

Chemistries

CartridgesSample + reagents

storage and processing

Instruments

Bioanalytical platforms.Integrated multi-disciplinary systems.

8Stig Morten Borch, pHealth2009 ICT

Lab-on-a-chipAllows for:

Completely self-contained system Disposable cassettes with all reagents included. Sealed compact format.

Micro-channels.High accuracy in liquid handling Operates small sample volumes Very little reagent necessary

Low cost productionFast assaysRobustness ..

Chemistries

Detectionsystems

Instruments

CartridgesSample +

assay processing

SINTEF equipment for polymer chip moldings (prototyping) SINTEF equipment for polymer chip moldings (prototyping)

9Stig Morten Borch, pHealth2009 ICT

Microfluidics allow for controlled liquid handling:

Filtering and active porous membranes

Exactmetering

Mixing

Splitting

ThinXXS design kit slides: microBUILDER

Microfluidic functionalities are readily combined with a variety of sensor and

actuator systems as well as a variety surface modifications (Bio-functional layers)

Silicon based microchips

Lysis buffer

Mixer 1

Mixer 2

Ethanol

Incubation chamber(21 µl)

Storage chamber(31µl)

Washing buffer 1

Waste

Product

Connections tosilicon chip

Washing buffer 2Elution buffer

Sample (blood)Sample storage loop(11µl)

Multifunctional slide for DNA extraction

www.microbuilder.orgwww.microbuilder.org

Reagent integrationExcellent, liquid and Excellent, liquid and gassgass barriersbarriers

OD- measurementsCuvette cavities

COC: excellent optical featuresCOC: excellent optical features

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Detectionsystems

Chemistries

Instruments

Chemistries and reagents:Biotechnology,Nanotechnology,Surface modification:Small volumes and fast assays =>Very fast interaction between reactants:

Reagent stability:Room temperature storage

Liquid and dried reagents formulations

CartridgesSample + assay

processing

OC2H5

C2H5O

OC2H5

OC2H5

OC2H5

OH Si

Si OH

CO

C (C

yclic

Ole

fin

Cop

olym

er)

Methanol / Water , 18h

OH

CO

C (C

yclic

Ole

fin

Cop

olym

er)

Immobilized Immobilized biomoleculesbiomolecules::•• MicroMicro--cavity wallscavity walls•• BeadsBeads•• Porous membranePorous membrane•• Microchip surfacesMicrochip surfaces

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Lab-on-a-chip cartridges may be operated by compact (handheld) instruments:

Signal read out:• Optics

• colours (OD), fluorescence, chemiluminescence

• Functionalized MEMS sensors• Electrochemical sensors• Integrated optical sensors• …….

Fluorescent readout of 10 chambers

Liquid processing:• Capillary forces• Pumps (Integrated or external) • Centrifugal forces• Electro-osmosis

Instruments

Detectionsystems

CartridgesSample +

assay processing

Chemistries

12Stig Morten Borch, pHealth2009 ICT

Detectionsystems

Chemistries

Cartridges

Instruments

Lab-on-a-chip / -disc• Microfluidics design• Prototype molding • High speed fluidic control • Sample + reagents processing

Micro-sensorsMicro-opticsHigh and low sensitivityWide range

• Integration• Automation• Miniaturation• Communication

• Assay design • Reagents preservation• Surface modification• Biotechnology

SINTEF; Cover all fields of competence necessary for developing reliable IVD platforms of the future:

SINTEF seek to utilize our broad and unique competences to further develop technologies in this field by direct collaboration with industry partners and

through international collaborative projects.

Through the microBUILDER consortium we have a network of volume production partners.